Timing of cognitive decline onset and life-course trajectories A pooled longitudinal analysis of 14,389 adults across three cohorts.
Overview
- Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Olomouc, Czech Republic
- Department of Psychology and Abnormal Psychology, Faculty of Education, Palacky University Olomouc, Olomouc, Czech Republic
- Department of Psychiatry, McGill University, Montreal, Canada
- MoCA Clinic and Institute, Quebec, Canada
- Department of Neurology, and the Franke Global Neuroscience Education Center, Barrow Neurological Institute, Phoenix AZ, USA
- Department of Neurology, Gloucestershire Hospitals NHS Foundation Trust, Gloucester, UK
Abstract
Background: Population ageing is driving a global surge in cognitive impairment. While late-life decline is well-characterized, the onset of measurable cognitive changes across the full adult lifespan remains uncertain. We aimed to estimate the age at which detectable decline begins using longitudinal data from three population-based cohorts from three countries spanning three continents.
Methods: We analyzed participant-level longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS; China), Midlife in the United States (MIDUS; USA), and Kardiovize (KV; Czech Republic). Cognitive performance was assessed using validated instruments (TICS, BTACT, and MoCA). Scores were harmonized using the percent of maximum possible method (0-100 metric). Linear mixed-effects models, adjusted for age group, sex, and education estimated change over an average 7–9-year follow-up.
Findings: In pooled sample of 14,389 participants (baseline age 22-94 years), a detectable decline in total cognition first emerged in the 31-40 age group (mean change -1.2 points, 95% CI -2.1 to -0.3). Decline magnitude increased progressively with age, reaching -11.4-points in the oldest strata (all p<0.001). Non-memory domains showed earlier vulnerability (detectable from age 31), while significant memory decline emerged after age 50. Individual trajectories showed substantial heterogeneity, suggesting that chronological age is not a deterministic proxy for decline.
Interpretation: Population-level cognitive decline became detectable in early midlife, decades before the traditional clinical focus on older age. Across three population-based cohorts from Asia, North America, and Europe, we observed consistent early decline in non-memory domains followed by later memory decline. These findings support evaluation of midlife cognitive monitoring and life-course approaches to brain health.
Funding: European Union Next Generation EU; European Regional Development Fund; European Social Fund; Barrow Neurological Foundation; NIH.
Reproduced under the paper's license (CC BY), from the paper cited above.
Code
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Data
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Data sharing
Access to participant-level data is subject to the data use agreements and governance policies of the original cohort studies: CHARLS (charls.pku.edu.cn), MIDUS (midus.wisc.edu), and KV. Derived analytical code and additional methodological details are available from the corresponding author on reasonable request, subject to institutional approvals. And data transfer agreements
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
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Version 3, 28 September 2026
- Funding: added Barrow Neurological Foundation; European Commission: LX22 NPO5107, CZ.02.1.01/0.0/0.0/16_019/0000868, CZ.02.1.01, 02.1.01/0.0/0.0, 02.1.01/0.0/0.0/16_019/0000868, CZ.02, CZ.02.1.01/0.0/0.0/16_019 /0000868, CZ.02.1.01/0.0, CZ.02.1.01/0.0/0.0, /16_019, LX22NPO5107; Ministerstvo Školství, Mládeže a Tělovýchovy: CZ.02.1.01/0.0/0.0/16_019, CZ.02.1.01/ 0.0/0.0/16_019/0000868, CZ.02, LX22NPO5107, CZ.02.1.01, CZ.02.1.01/0.0; National Institutes of Health: LX22NPO5107
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 7 keywords, 72 references.
Cite
This paper
Novotný, J. S., Klil-Drori, S., Geda, Y. E., Nasreddine, Z., & Stokin, G. B. (2026). Timing of cognitive decline onset and life-course trajectories A pooled longitudinal analysis of 14,389 adults across three cohorts. The journal of prevention of Alzheimer's disease, 13(9), 100649. https://
BibTeX
@article{novotny2026timi
author = {Novotný, Jan Sebastian and Klil-Drori, Sivan and Geda, Yonas Endale and Nasreddine, Ziad and Stokin, Gorazd Bernard},
title = {{Timing of cognitive decline onset and life-course trajectories A pooled longitudinal analysis of 14,389 adults across three cohorts}},
journal = {The journal of prevention of Alzheimer's disease},
year = {2026},
month = aug,
volume = {13},
number = {9},
pages = {100649},
publisher = {Elsevier},
issn = {2426-0266},
doi = {10.1016/
url = {https://
pmid = {42566820},
pmcid = {PMC13475508}
}
RIS
TY - JOUR
AU - Novotný, Jan Sebastian
AU - Klil-Drori, Sivan
AU - Geda, Yonas Endale
AU - Nasreddine, Ziad
AU - Stokin, Gorazd Bernard
TI - Timing of cognitive decline onset and life-course trajectories A pooled longitudinal analysis of 14,389 adults across three cohorts
T2 - The journal of prevention of Alzheimer's disease
J2 - J Prev Alzheimers Dis
PY - 2026
DA - 2026/
VL - 13
IS - 9
SP - 100649
SN - 2426-0266
PB - Elsevier
DO - 10.1016/
UR - https://
LA - en
ER -
CSL-JSON
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